This project seeks to identify and develop a new generation of drugs that will mimic the action of glucocorticoids in immune cells, while avoiding the many serious side effects of glucocorticoids in non-immune cells. Glucocorticoids have been in clinical use since the late 1940s. They remain among the most frequently prescribed drugs worldwide. They are used as the first line of attack in many inflammatory and autoimmune conditions, due to their potent and rapid anti-inflammatory and immunosuppressive effects. However, they also have a long list of serious, dose-limiting side effects involving every organ system. Initial work at Dr. Franco lab has identify specific cell lines to carry out the high-throughput assays and evaluate them in 96-well results on 384-well plate toward identification of TNFa directly on the cell-culture plate by direct antibody addition. NCGC will be working to further miniaturize this assay to 1536-well format, and once validated, carry out the high-throughput screen.